Dendrimer-based macromolecular conjugate for the kidney-directed delivery of a multitargeted sunitinib analogue

M. E Emmy M Dolman, Kim M A van Dorenmalen, Ebel H E Pieters, Rolf W. Sparidans, Marie Lacombe, Bálint Szokol, L. Őrfi, G. Kéri, Niels Bovenschen, Gert Storm, Wim E. Hennink, Robbert J. Kok

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The development of a macromolecular conjugate of a multitargeted tyrosine kinase inhibitor is described that can be used for renal-specific delivery into proximal tubular cells. A novel sunitinib analogue, that is, 17864, is conjugated to a NH 2-PAMAM-G3 dendrimer via the platinum (II)-based Universal Linkage System (ULS™). The activity of 17864 is retained after coordination to the ULS linker alone or when coupled to NH 2-PAMAM-G3. 17864-UlS-NH 2-PAMAM-G3 is non-toxic to proximal tubular cells in vitro. After intravenous administration to mice, 17864-UlS-NH 2-PAMAM-G3 rapidly and efficiently accumulates in the kidneys. These results are encouraging for future studies focusing on the development of novel therapeutics for the treatment of renal diseases.

Original languageEnglish
Pages (from-to)93-103
Number of pages11
JournalMacromolecular Bioscience
Volume12
Issue number1
DOIs
Publication statusPublished - Jan 2012

Fingerprint

Dendrimers
Platinum
Protein-Tyrosine Kinases
Kidney
Intravenous Administration
Therapeutics
sunitinib

Keywords

  • Dendrimers
  • Drug delivery systems
  • Kidney
  • Platinum linkers
  • Sunitinib

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomaterials
  • Polymers and Plastics
  • Materials Chemistry

Cite this

Dolman, M. E. E. M., van Dorenmalen, K. M. A., Pieters, E. H. E., Sparidans, R. W., Lacombe, M., Szokol, B., ... Kok, R. J. (2012). Dendrimer-based macromolecular conjugate for the kidney-directed delivery of a multitargeted sunitinib analogue. Macromolecular Bioscience, 12(1), 93-103. https://doi.org/10.1002/mabi.201100277

Dendrimer-based macromolecular conjugate for the kidney-directed delivery of a multitargeted sunitinib analogue. / Dolman, M. E Emmy M; van Dorenmalen, Kim M A; Pieters, Ebel H E; Sparidans, Rolf W.; Lacombe, Marie; Szokol, Bálint; Őrfi, L.; Kéri, G.; Bovenschen, Niels; Storm, Gert; Hennink, Wim E.; Kok, Robbert J.

In: Macromolecular Bioscience, Vol. 12, No. 1, 01.2012, p. 93-103.

Research output: Contribution to journalArticle

Dolman, MEEM, van Dorenmalen, KMA, Pieters, EHE, Sparidans, RW, Lacombe, M, Szokol, B, Őrfi, L, Kéri, G, Bovenschen, N, Storm, G, Hennink, WE & Kok, RJ 2012, 'Dendrimer-based macromolecular conjugate for the kidney-directed delivery of a multitargeted sunitinib analogue', Macromolecular Bioscience, vol. 12, no. 1, pp. 93-103. https://doi.org/10.1002/mabi.201100277
Dolman, M. E Emmy M ; van Dorenmalen, Kim M A ; Pieters, Ebel H E ; Sparidans, Rolf W. ; Lacombe, Marie ; Szokol, Bálint ; Őrfi, L. ; Kéri, G. ; Bovenschen, Niels ; Storm, Gert ; Hennink, Wim E. ; Kok, Robbert J. / Dendrimer-based macromolecular conjugate for the kidney-directed delivery of a multitargeted sunitinib analogue. In: Macromolecular Bioscience. 2012 ; Vol. 12, No. 1. pp. 93-103.
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